JP2018529650A5 - - Google Patents

Claims (21)

  In the manufacture of a medicament for the treatment of stroke and traumatic brain injury, a therapeutically effective amount of a compound having the structure of formula (II), or a pharmaceutically acceptable salt or pharmaceutically acceptable thereof The use of solvates:
In the formula:
  R ’ ₁ Is
Is;
  L ₂ Is —NH—C (═O) —, or —C (═O) NH—;
  X is CR ₃ Or N;
  Y is CR ₉ Or selected independently from N;
  R ₂ Is C ₁ -C ₆ Alkyl, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₆ Heteroalkyl, C ₁ -C ₆ Haloalkyl, C ₂ -C ₈ Heterocycloalkyl, C ₁ -C ₄ Alkylene C ₂ -C ₈ Heterocycloalkyl, aryl, heteroaryl, fused aryl or fused heteroaryl; where C ₁ -C ₆ Alkyl, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₆ Heteroalkyl, C ₁ -C ₆ Haloalkyl, C ₂ -C ₈ Heterocycloalkyl, C ₁ -C ₄ Alkylene C ₂ -C ₈ Heterocycloalkyl, aryl, heteroaryl, fused aryl or fused heteroaryl is at least one R ₃ Optionally substituted with;
  R ₃ Are H, F, D, Cl, Br, I, -CN, -NO ₂ , -OH, -CF ₃ , -OCF ₃ , -OR ₅ , C ₁ -C ₆ Alkyl, C ₃ -C ₈ Cycloalkyl, C ₁ -C ₆ Heteroalkyl, C ₁ -C ₆ Haloalkyl, C ₂ -C ₈ Independently selected from heterocycloalkyl, optionally substituted aryl, optionally substituted O-aryl, optionally substituted heteroaryl,
  n is an integer selected from 0-2;
  R ₉ H, D, halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, -OR ₅ , -OCF ₃ , C ₁ -C ₆ Carbonyl alkyl or -CF ₃ Or two R bonded to the same carbon atom ₉ Forms an oxetane ring;
  R ₁₀ Is halogen, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, -OR ₅ , -OCF ₃ , C ₁ -C ₆ Carbonyl alkyl or -CF ₃ Selected from;
  R ₅ H, C ₁ -C ₆ Alkyl, C ₁ -C ₆ Haloalkyl, C ₃ -C ₈ Use, independently selected from cycloalkyl, phenyl, and benzyl.   The use according to claim 1, wherein X is CH.   R ’ ₁ But
The use according to claim 1 or 2, wherein Y is CH.   R ₂ But at least one R ₃ 4. Use according to any one of claims 1-3, which is phenyl substituted with.   R ₂ Is Cl, Br, F, I, CF ₃ , C ₁ -C ₆ Alkyl or OC ₁ -C ₆ At least one R selected from alkyl ₃ 5. Use according to any one of claims 1-4, which is phenyl substituted with.   R ₂ Are Cl, F, and CH ₃ At least one R selected from ₃ 6. Use according to any one of claims 1-5, which is phenyl substituted with.   R ₂ 7. Use according to any one of claims 1-6, wherein is phenyl substituted with at least one F.   At least one R ₉ 8. Use according to any one of claims 1-7, wherein is halogen.   R ’ ₁ But,
The use according to any one of claims 1 to 8, wherein n is 0.   R ₁₀ Is halogen or C ₁ -C ₆ 10. Use according to any one of claims 1-9, which is alkyl.   R ₁₀ 11. Use according to any one of claims 1-10, wherein is Cl.   R ₁₀ Is -CH ₃ 11. Use according to any one of claims 1-10, wherein   R ₁₀ Is -CH ₂ CH ₃ 11. Use according to any one of claims 1-10, wherein   R ₂ But two R ₃ Phenyl substituted by ₃ Is F and one R ₃ Is CH ₃ 14. Use according to any one of claims 1-13, which is   R ₂ But two R ₃ Phenyl substituted by ₃ Is F and one R ₃ 15. Use according to claim 14, wherein is Cl.   R ₂ But two R ₃ Phenyl substituted with ₃ 15. Use according to claim 14, wherein each is F.   R ₂ But three R ₃ Phenyl substituted with ₃ 14. Use according to any one of claims 1-13, wherein each is F.   R ₂ But at least one R ₃ 4. Use according to any one of claims 1-3, which is heteroaryl substituted with.   19. Use according to claim 18, wherein heteroaryl is pyridyl.   R ₂ Is Cl, Br, F, I, CF ₃ , C ₁ -C ₆ Alkyl or OC ₁ -C ₆ At least one R selected from alkyl ₃ 19. Use according to claim 18 which is heteroaryl substituted with.   L ₂ 21. Use according to any one of claims 1-20, wherein is -NH-C (= O)-.